Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses
Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types a...
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doaj-5f530ff309a2440cb8f6900faa1fad972021-07-14T09:59:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.691758691758Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 VirusesIrina Nudelman0Irina Nudelman1Daniil Kudrin2German Nudelman3Raamesh Deshpande4Boris M. Hartmann5Boris M. Hartmann6Steven H. Kleinstein7Chad L. Myers8Chad L. Myers9Stuart C. Sealfon10Stuart C. Sealfon11Elena Zaslavsky12Elena Zaslavsky13Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of General Internal Medicine, New York University Langone Medical Centre, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Computer Science and Engineering, University of Minnesota - Twin Cities, Minneapolis, MN, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays (CARDA), Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Pathology, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Computer Science and Engineering, University of Minnesota - Twin Cities, Minneapolis, MN, United StatesProgram in Biomedical Informatics and Computational Biology, University of Minnesota - Twin Cities, Minneapolis, MN, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays (CARDA), Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays (CARDA), Icahn School of Medicine at Mount Sinai, New York, NY, United StatesInfluenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity.https://www.frontiersin.org/articles/10.3389/fimmu.2021.691758/fulltranscriptional profiletemporal dynamicsmodule discoveryconserved and differential modulesInfluenza H1N1differential regulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Irina Nudelman Irina Nudelman Daniil Kudrin German Nudelman Raamesh Deshpande Boris M. Hartmann Boris M. Hartmann Steven H. Kleinstein Chad L. Myers Chad L. Myers Stuart C. Sealfon Stuart C. Sealfon Elena Zaslavsky Elena Zaslavsky |
spellingShingle |
Irina Nudelman Irina Nudelman Daniil Kudrin German Nudelman Raamesh Deshpande Boris M. Hartmann Boris M. Hartmann Steven H. Kleinstein Chad L. Myers Chad L. Myers Stuart C. Sealfon Stuart C. Sealfon Elena Zaslavsky Elena Zaslavsky Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses Frontiers in Immunology transcriptional profile temporal dynamics module discovery conserved and differential modules Influenza H1N1 differential regulation |
author_facet |
Irina Nudelman Irina Nudelman Daniil Kudrin German Nudelman Raamesh Deshpande Boris M. Hartmann Boris M. Hartmann Steven H. Kleinstein Chad L. Myers Chad L. Myers Stuart C. Sealfon Stuart C. Sealfon Elena Zaslavsky Elena Zaslavsky |
author_sort |
Irina Nudelman |
title |
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses |
title_short |
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses |
title_full |
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses |
title_fullStr |
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses |
title_full_unstemmed |
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses |
title_sort |
comparing host module activation patterns and temporal dynamics in infection by influenza h1n1 viruses |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-07-01 |
description |
Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity. |
topic |
transcriptional profile temporal dynamics module discovery conserved and differential modules Influenza H1N1 differential regulation |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.691758/full |
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